4-[(arylmethyl)aminomethyl]piperidine derivatives, their preparation and their therapeutic application

1. A compound of formula (I):

wherein:

n is 1 or 2;

R 1 is trifluoromethyl;

R 2 is hydrogen or (C 1 -C 3 )alkyl;

R 3 is an aromatic group selected from:

wherein the aromatic group is unsubstituted or mono- or disubstituted by a substituent selected independently from halogen, (C 1 -C 3 )alkyl or (C 1 -C 3 )alkoxy; and

R 4 is hydrogen or (C 1 -C 3 )alkyl;

or an addition salt with an acid thereof.

2. The compound according to claim 1 , wherein:

n is 1;

or an addition salt with an acid thereof.

3. The compound according to claim 1 , wherein:

R 1 is in position 3 of the phenyl and is trifluoromethyl;

or an addition salt with an acid thereof.

4. The compound according to claim 1 , wherein:

R 2 is hydrogen or methyl;

or an addition salt with an acid thereof.

5. The compound according to claim 1 , wherein:

R 3 is 1-methyl-1H-pyrrol-2-yl; 1-methyl-1H-imidazol-2-yl; 1,3-thiazol-2-yl; 2-furyl; 3-furyl; 5-methyl-2-furyl; 4,5-dimethyl-2-furyl; 5-chloro-2-furyl; 2-thienyl; 3-thienyl; phenyl; pyridin-2-yl; pyridin-3-yl; pyridin-4-yl; pyrazin-2-yl; 6-methylpyridin-2-yl; 3-methyl-2-thienyl; 5-methyl-2-thienyl; pyrimidin-5-yl; 1H-imidazol-2-yl; 1H-imidazol-5-yl; or 4-methyl-1H-imidazol-5-yl; or an addition salt with an acid thereof.

6. The compound according to claim 1 , wherein:

n is 1;

R 1 is in position 3 of the phenyl and is trifluoromethyl;

R 2 is hydrogen or methyl; and

R 3 is 1-methyl-1H-pyrrol-2-yl; 1-methyl-1H-imidazol-2-yl; 1,3-thiazol-2-yl; 2-furyl; 3 -furyl; 5-methyl-2-furyl; 4,5-dimethyl-2-furyl; 5-chloro-2-furyl; 2-thienyl; 3-thienyl; phenyl; pyridin-2-yl; pyridin-3-yl; pyridin-4-yl; pyrazin-2-yl; 6-methylpyridin-2-yl; 3-methyl-2-thienyl; 5-methyl-2-thienyl; pyrimidin-5-yl; 1H-imidazol-2-yl; 1H-imidazol-5-yl; or 4-methyl-1H-imidazol-5-yl; or an addition salt with an acid thereof.

7. A process for preparing the compound according to claim 1 , comprising:

reacting a compound of formula (II)

wherein n, R 1 and R 2 are as defined in claim 1 , with a compound of formula (III)

wherein R 3 is as defined in claim 1 , in the presence of an acid and in a solvent to form an iminium salt, and reducing the iminium salt by a reducing agent.

8. A pharmaceutical composition comprising the compound according to claim 1 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising the compound according to claim 2 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising the compound according to claim 3 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

11. A pharmaceutical composition comprising the compound according to claim 4 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

12. A pharmaceutical composition comprising the compound according to claim 5 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

13. A pharmaceutical composition comprising the compound according to claim 6 , or an addition salt with an acid thereof, and at least one pharmaceutically acceptable excipient.

14. A method for treating chronic neuropathic or inflammatory pain in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 , or an addition salt with an acid thereof.